Throughout this application, various publications are referenced by author and date. Full citations for these publications may be found listed alphabetically at the end of the specification immediately preceding Sequence Listing and the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
An important means by which tumors grow and invade surrounding normal tissue is by a complex series of cellxe2x80x94cell and cell matrix interactions. We have focused on the interaction of tumor cells with matrix-associated components. The Receptor to AGE (RAGE) interacts with a range of physiologically and pathophysiologically-relevant ligands (1-5). In normal developing neurons of the central nervous system, the expression of RAGE is markedly enhanced and co-localizes with that of its ligand, amphoterin. Amphoterin, a matrix-associated polypeptide, is expressed in developing neurons and certain tumor cells, such as rat C6 glioma cells (6-12).
The present invention provides for a method for inhibiting tumor invasion or metastasis in a subject which comprises administering to the subject a therapeutically effective amount of a form of soluble Receptor for Advanced Glycation Endproducts (RAGE). The present invention also provides a method for evaluating the ability of an agent to inhibit tumor invasion in a local cellular environment which comprises: (a) admixing with cell culture media an effective amount of the agent; (b) contacting a tumor cell in cell culture with the media from step (a); (c) determining the amount of spreading of the tumor cell culture, and (d) comparing the amount of spreading of the tumor cell culture determined in step (c) with the amount determined in the absence of the agent, thus evaluating the ability of the agent to inhibit tumor invasion in the local cellular environment. The present invention also provides a pharmaceutical composition which comprises a therapeutically effective amount of the agent evaluated in the aforementioned method and a pharmaceutically acceptable carrier.